Alzheimer's disease (AD), the most common form of dementia seen in clinical practice, is a progressive, terminal, neurodegenerative disorder. The largest risk factor for Alzheimer disease (AD) is advanced age, and the public health impact of AD and related disorders is increasing in proportion to the increasing numbers of elderly. Alzheimer disease presents clinically as progressive memory loss but the only definitive diagnostic tests that now exist require neuropathologic examination of brain tissue, conducted almost exclusively postmortem.
As knowledge of the molecular features of AD and related neurodegenerative disorders advances, strategies for pharmaceutical interventions that implement this knowledge are being vigorously pursued [Irizarry et al., 2001]. However, there is currently no method for monitoring pathogenic response to such interventions in human clinical trials or for definitively diagnosing these disorders at an early stage, when intervention could be most beneficial.
There are now numerous articles documenting efforts to apply conventional medical imaging techniques to the diagnosis and monitoring of AD [Coimbra et al., 2006]. Magnetic resonance imaging (MRI) has provided a wealth of functional [Malchulda et al., 2003] and anatomic [Jack et al., 2005] information. The development of radionuclide markers targeting parenchymal amyloid deposits is a breakthrough in the application of positron emission tomography (PET) [Mathis et al., 2004]. And optical techniques, while not yet as widely applied in clinical practice as MRI or PET, have made parallel contributions to these efforts, utilizing functional information [Hock et al., 1997; Strangman et al., 2002] or exogenous markers in mice [Hintersteiner et al., 2005; Skoch et al.].
The expression “near-infrared window” describes the biomedically useful property of near-infrared light [Jobsis-vander Vliet, 1999] that it can propagate harmlessly several centimeters through living tissue and provide diagnostically valuable physical and chemical information by means of spectroscopic analysis [Jobsis, 1977].
The definitive neuropathologic features that distinguish a brain damaged from Alzheimer's Disease (AD) from normal brain (non-AD), are neuritic plaques (NP) and neurofibrillary tangles (NFT). Neuritic plaques are predominantly extra-cellular deposits of β-amyloid peptide fibrils and NFT are intra-neuronal accumulations of abnormally phosphorylated and oxidized tau protein. Currently, definitive diagnosis of Alzheimer disease relies upon postmortem detection of cortical neuritic plaques and neurofibrillary tangles [Love, 2005]. Routinely, histological sectioning and staining are required to detect these structures against the neuropil background.
Perelman (1998) described a non-invasive optical spectroscopy technique to detect dysplasia in Barrett's esophagus based on light scattering by epithelial cell nuclei.
There remains a need for non-invasively detecting brain disease or injury (including Alzheimer disease) in vivo.